Acrivastine

R06A - Antihistamines for systemic use ATC R06AX18 Small molecule approved 1994 Oral Natural product

JFDA label: Semprex Capsules

Mechanism of Action

Antagonist of Histamine H1 receptor — Histamine H1 receptor antagonist

Target	Action	Gene / class
Histamine H1 receptor efficacy	ANTAGONIST	HRH1

Indications

Approved

Hypersensitivity — allergic disease

Contraindications

Source: Lexicomp

Hypersensitivity to pseudoephedrine, acrivastine, other alkylamine antihistamines such as chlorpheniramine, or any component of the formulation Absolute
severe hypertension, severe coronary artery disease Absolute
use with or within 14 days of MAO inhibitors Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (3)

Common dizziness · Insomnia · nervousness

Renal and urinary disorders (1)

Common Dysmenorrhea

Gastrointestinal disorders (3)

Common dyspepsia · nausea · Xerostomia

Other (2)

Very Common Central nervous system: Headache · drowsiness

Respiratory, thoracic and mediastinal disorders (2)

Common cough · Pharyngitis

Dosing

Source: Lexicomp

Seasonal allergic rhinitis: Oral: Acrivastine 8 mg/pseudoephedrine 60 mg: One capsule every 4 to 6 hours (maximum: 4 doses/24 hours)

Seasonal allergic rhinitis: Children ≥12 years and Adolescents: Oral: Refer to adult dosing.

Refer to adult dosing.

Avoid use in patients with CrCl ≤48 mL/minute.

There are no dosage adjustments recommended in manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:

Cardiovascular disease

Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease); contraindicated with severe disease.

Diabetes

Use with caution in patients with diabetes mellitus.

Increased intraocular pressure/glaucoma

Use with caution in patients with increased intraocular pressure or glaucoma.

Prostatic hyperplasia/urinary obstruction

Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

Pyloroduodenal obstruction

Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer).

Renal impairment

Use with caution in patients with renal impairment; avoid use in patients with CrCl ≤48 mL/minute.

Thyroid dysfunction

Use with caution in patients with thyroid dysfunction. Concurrent drug therapy issues:

Sedatives

Effects may be potentiated when used with other sedative drugs or ethanol. Special populations:

Elderly

Use with caution in the elderly; may be more sensitive to adverse effects.

Pregnancy & Lactation

Pregnancy

FDA category B Teratogenic

Teratogenic effects were not observed in animal reproduction studies with this combination; therefore, the manufacturer classifies acrivastine/pseudoephedrine as pregnancy category B. The use of antihistamines for the treatment of rhinitis during pregnancy is generally considered to be safe at recommended doses. Information related to the use of acrivastine during pregnancy is limited; therefore, other agents are preferred. Also refer to the Pseudoephedrine monograph for additional information.

Lactation

It is not known if acrivastine is excreted into breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy with this combination product should take into account the risk of exposure to the infant and the benefits of treatment to the mother. Pseudoephedrine is excreted into breast milk; refer to the Pseudoephedrine monograph for additional information.

Chemistry & Properties

Formula	C22H24N2O2
Molecular weight	348.45 g/mol
IUPAC name	(E)-3-[6-[(E)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]-2-pyridinyl]prop-2-enoic acid
CAS	87848-99-5
PubChem CID	5284514
InChIKey	`PWACSDKDOHSSQD-IUTFFREVSA-N`
logP	4.02 (XLogP 1.6)
Polar surface area	53.43 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.80
Lipinski violations	0

SMILES

Cc1ccc(/C(=C\CN2CCCC2)c2cccc(/C=C/C(=O)O)n2)cc1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No (logBB -1.14)

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Potassium chloride	major
Potassium citrate	major
Sodium oxybate	major
Topiramate	major
Zonisamide	major
Acetylcholine	moderate
Aclidinium	moderate
Alimemazine	moderate
Amantadine	moderate
Amitriptyline	moderate
Amoxapine	moderate
Apomorphine	moderate
Apraclonidine	moderate
Aripiprazole	moderate
Asenapine	moderate
Atropine	moderate
Azatadine	moderate
Belladonna	moderate
Benzatropine	moderate
Biperiden	moderate
Botulinum Toxin Type B	moderate
Botulinum toxin type A	moderate
Brexanolone	moderate
Brexpiprazole	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Brompheniramine	moderate
Candida albicans	moderate
Carbamoylcholine (ophthalmic)	moderate
Carbinoxamine	moderate
Cariprazine	moderate
Chlorcyclizine	moderate
Chlorpheniramine	moderate
Chlorpromazine	moderate
Clemastine	moderate
Clidinium	moderate
Clomipramine	moderate
Clozapine	moderate
Coccidioides immitis spherule	moderate
Cyclizine	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Semprex Capsules	Capsule 8 mg	24 cap	Suleiman Tannous & Sons Co. Ltd	1.640